CD3E

Protein identityUniProt · HPA

UniProt accession

P07766

Gene

CD3E

Ensembl

ENSG00000198851

Chromosome

11

Canonical length

207 aa

Protein class

CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Predicted membrane proteins, Transporters

Subcellular location

Endoplasmic reticulum,Golgi apparatus,Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is the CD3-epsilon polypeptide, which together with CD3-gamma, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T-cell receptor-CD3 complex. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The genes encoding the epsilon, gamma and delta polypeptides are located in the same cluster on chromosome 11. The epsilon polypeptide plays an essential role in T-cell development. Defects in this gene cause immunodeficiency. This gene has also been linked to a susceptibility to type I diabetes in women. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

207 residues, UniProt reviewed canonical sequence.

>P07766|CD3E
     1  MQSGTHWRVL GLCLLSVGVW GQDGNEEMGG ITQTPYKVSI SGTTVILTCP QYPGSEILWQ
    61  HNDKNIGGDE DDKNIGSDED HLSLKEFSEL EQSGYYVCYP RGSKPEDANF YLYLRARVCE
   121  NCMEMDVMSV ATIVIVDICI TGGLLLLVYY WSKNRKAKAK PVTRGAGAGG RQRGQNKERP
   181  PPVPNPDYEP IRKGQRDLYS GLNQRRI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CD3E can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.51

Highest tissue expression

596 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CD3E.

Disease | AllUniProt

Conditions CD3E is implicated in, by any mechanism.

• Immunodeficiency 18 (IMD18) MIM:615615

Disease | GeneticClinVar

21 pathogenic / likely-pathogenic of 300 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Immunodeficiency 18
• Immunodeficiency 18, severe combined immunodeficiency variant
• Severe combined immunodeficiency disease

ReferencesPubMed · IEDB

Publications for CD3E from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.92

gnomAD pLI

0

gnomAD missense Z

0.3

DepMap mean gene effect

0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adaptive immune response
• alpha-beta T cell activation
• apoptotic signaling pathway
• calcium-mediated signaling
• CD4-positive, alpha-beta T cell proliferation
• cell surface receptor protein tyrosine kinase signaling pathway
• cell surface receptor signaling pathway
• cerebellum development
• dendrite development
• G protein-coupled receptor signaling pathway
• gamma-delta T cell activation
• negative regulation of gene expression
• negative regulation of smoothened signaling pathway
• negative thymic T cell selection
• positive regulation of calcium-mediated signaling
• positive regulation of CD4-positive, alpha-beta T cell proliferation
• positive regulation of cell-cell adhesion mediated by integrin
• positive regulation of cell-matrix adhesion
• positive regulation of gene expression
• positive regulation of interleukin-2 production
• positive regulation of interleukin-4 production
• positive regulation of T cell anergy
• positive regulation of T cell proliferation
• positive regulation of type II interferon production
• positive thymic T cell selection
• protein-containing complex assembly
• regulation of apoptotic process
• signal complex assembly
• smoothened signaling pathway
• T cell activation
• T cell anergy
• T cell costimulation
• T cell receptor signaling pathway

Molecular functions

• identical protein binding
• protein kinase binding
• protein-macromolecule adaptor activity
• SH3 domain binding
• signaling receptor complex adaptor activity
• T cell receptor binding
• transmembrane signaling receptor activity

Cellular components

• alpha-beta T cell receptor complex
• cell body
• cell-cell junction
• dendritic spine
• endoplasmic reticulum
• external side of plasma membrane
• gamma-delta T cell receptor complex
• Golgi apparatus
• immunological synapse
• plasma membrane
• T cell receptor complex

Protein domainsUniProt · Pfam · InterPro

• Phosphorylated immunoreceptor signalling ITAM
• Immunoglobulin subtype 2
• Immunoglobulin-like fold
• CD3 protein, epsilon/gamma/delta subunit
• Immunoglobulin-like domain superfamily
• Immunoreceptor tyrosine-based activation motif
• Ig-like domain on T-cell surface glycoprotein CD3 epsilon chain

KeywordsUniProt

• Adaptive immunity
• Cell membrane
• Disulfide bond
• Immunity
• Immunoglobulin domain
• Membrane
• Phosphoprotein
• Receptor
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CD3E in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CD6
• NUMB
• DENND1B
• CEACAM1
• POLR1G
• LAG3
• EPS8L1
• NCK1
• NCK2